The determination of the activity of creatine kinase (abbreviated herein to CK, but also known as creatine phosphokinase, and CPK) is useful in the diagnosis of diseases such as progressive muscular dystrophy, dermatomyositis, and myocardial infarctions. CK occurs in human body fluids and tissue in the form of different isoenzymes: for example, CK-MM in muscles, CK-BB in the brain, and CK-MB in the myocardium. The CK activity occurring in healthy human blood serum is normally due to the CK-MM isoenzyme, because CK-BB does not generally pass into the blood stream. In a healthy individual, the CK-MB is generally restricted to certain organs, e.g. the myocardium. However, when the myocardium is damaged, as in the case of a cardiac infarction, CK-MB is released into the blood serum and can be detected therein.
Clinical devices which determine the amount of CK or CK-MB in serum require calibration as well as frequent quality control to indicate whether the diagnostic device is in proper operation. Compositions used for such quality control or calibration (hereafter control compositions) contain a known activity of the enzyme to be assayed. It is axiomatic that the enzyme activity of such controls not change substantially over time. Further, it is important that the enzyme present in the control composition behave in the same way as the enzyme present in the patient sample.
Some attempts to protect enzymes such as creatine kinase against loss of activity focus primarily on modifying the enzyme itself in some way. U.S. Pat. No. 4,931,392, for example, teaches, a two-step method comprising (a) disulfide modification of the enzyme, and (b) covalently binding an activated carbohydrate to creatine kinase.
The problem with this approach is that the control enzyme is altered and is therefore different from the native enzyme found in human sera. In this altered form, the enzyme might not behave or react like the native physiologically active enzyme and therefore might not be predictive of the enzyme activity in the patient sample. Such differences could lead to inaccurate results. Further, such altered enzymes are not commerically available and their preparation would increase the overall cost of the assay.